[Assessment of driving in patients with vertigo and dizziness]. / Fahreignungsbeurteilung bei Schwindel aus neurologischer Sicht.

The driving performance of patients with dizziness and vertigo has gained only minor attention so far. Patients with permanent vestibular loss or with episodic vestibular symptoms can experience difficulties in driving a motor vehicle. The presence of a chronic or episodic syndrome presenting with dizziness and/or vertigo does not automatically exclude the ability to drive. Assessment of driving performance should consider the degree of the deficits and compensation in chronic dysfunction and the severity and frequency of attacks, prodromes and triggers of symptoms in episodic disorders.

Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type disorders in mice.

The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that CD4+ T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.

[Traffic medicine expert opinions in otorhinolaryngology: current aspects]. / Verkehrsmedizinische Begutachtung in der HNO-Heilkunde : Aktuelle Aspekte.

According to German law granting of driving licenses depends on the proof of an adequate driving capability. The corresponding guidelines are at present in the process of being revised. At the moment bilateral deafness and high-grade hearing loss (> or = 60% in pure tone audiometry) are not exclusion criteria for driving licenses grades A, B and C, while driving licenses grade D and licenses for public transport are generally excluded. In the forthcoming revised edition of the guidelines it has been suggested that the latter group will also not be excluded. The regulations concerning dizziness are wide-sweeping at the moment as no driving license will be granted if dizziness is present but will be more specific in the next issue. In particular a division will be made between single axle and two axle vehicles. An expert assessment about driving suitability can only be made by a certified specialist with qualifications in traffic medicine.

Screening for Menière's disease in the general population - the needle in the haystack.

CONCLUSION: Based on clinical history alone, 98.4% of the population with vestibular vertigo do not qualify for a diagnosis of Menière's disease (MD). Although frequent in dizziness clinics, MD is rare in the general population. OBJECTIVE: To narrow down the prevalence of MD in the general population. SUBJECTS AND METHODS: A representative sample adult population sample (n=4869) was screened for moderate or severe dizziness/vertigo. Subsequently, 1003 participants completed a validated neurotologic telephone interview on vestibular vertigo (VV). Prevalence of MD was determined by stepwise application of clinical criteria according to the AAO (1995): (1) at least two vertigo attacks of > or =20 min duration, (2) unilateral hearing loss, and (3) accompanying cochlear symptoms. RESULTS: Lifetime prevalence of VV was 7.4%. Of 243 participants with VV, 51 (21%) had recurrent vertigo lasting > or =20 min. Of these, nine reported unilateral hearing loss, and four had accompanying cochlear symptoms (1.6% of VV patients, population prevalence 0.12%).

Epidemiology of benign paroxysmal positional vertigo: a population based study.

OBJECTIVES: To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. METHODS: Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting <1 min without concomitant neurological symptoms and invariably provoked by typical changes in head position. In a concurrent validation study (n = 61) conducted in two specialised dizziness clinics, BPPV was detected by our telephone interview with a specificity of 92% and a sensitivity of 88% (positive predictive value 88%, negative predictive value 92%). RESULTS: BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. CONCLUSION: BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.

Short-term efficacy of Epley's manoeuvre: a double-blind randomised trial.

BACKGROUND: Benign paroxysmal positional vertigo of the posterior canal (PC-BPPV) is a common vestibular disorder and can be easily treated with Epley's manoeuvre. Thus far, the short-term efficacy of Epley's manoeuvre for treatment of PC-BPPV is unknown. OBJECTIVES: To evaluate the efficacy of Epley's manoeuvre for treatment of PC-BPPV 24 h after applying the manoeuvre. METHODS: The short-term efficacy of Epley's manoeuvre was compared with a sham procedure in 66 patients with PC-BPPV by using a double-blind randomised study design. RESULTS: 24 h after treatment, 28 of 35 (80%) patients in the Epley's manoeuvre group had neither vertigo nor nystagmus on positional testing compared with 3 of 31 (10%) patients in the sham group (p<0.001). CONCLUSION: Epley's manoeuvre is shown to resolve PC-BPPV both effectively and rapidly.

Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors.

Serum antibodies reacting with the tumor suppressor protein p53 have been detected previously in cancer patients with a variety of neoplasms. Two initial (although insufficient) prerequisites for a B-cell response to occur have been proposed: p53 protein accumulation in the tumor or a mutant p53 gene, or both. We have examined 65 esophageal cancer cases (42 from Guangzhou and Shenyang, People's Republic of China, and 23 from Paris, France) to obtain a prevalence estimate of anti-p53 antibodies for this type of cancer and to define the relationship of p53 tumor status to B-cell immune response. Sera were analyzed in a triplicate assay (enzyme-linked immunoassay, immunoprecipitation, and immunoblot) for anti-p53 antibodies. Tumor DNA was screened for mutations in exons 5-8, and tumor tissue was examined by immunohistochemistry for abnormal p53 protein accumulation. p53 mutations were found in 36 (58%) of 62 cases analyzed. Sixteen patients (25%) had circulating antibodies to the tumor suppressor protein. All but two (88%) of the tumors from seropositive cases had a mutation in the DNA binding region of the p53 gene, and with one exception, these tumors also showed nuclear accumulation of the p53 protein. In contrast, tumor mutations were found in just 22 (46%) of the 48 individuals in whom we did not detect anti-p53 antibodies. Among the 22 seronegative cases for which we found no tumor mutations, 11 revealed p53 protein accumulation by immunohistochemical analysis. Thus, circulating anti-p53 antibodies may be present in one-fourth of esophageal cancer patients, most of whom also would be expected to have a p53 gene mutation in their tumors. Patients without such mutations appear considerably less likely to mount a B-cell response to the p53 tumor suppressor protein than those that do (P < 0.01).

Vestibular migraine.

During the last decades a new vestibular syndrome has emerged that is now termed vestibular migraine (VM). The main body of evidence for VM is provided by epidemiologic data demonstrating a strong association between migraine and vestibular symptoms. Today, VM is recognized as one of the most common causes of episodic vertigo. The clinical presentation of VM is heterogeneous in terms of vestibular symptoms, duration of episodes, and association with migrainous accompaniments. Similar to migraine, there is no clinical or laboratory confirmation for VM and the diagnosis relies on the history and the exclusion of other disorders. Recently, diagnostic criteria for VM have been elaborated jointly by the International Headache Society and the Bárány Society. Clinical examination of patients with acute VM has clarified that the vast majority of patients with VM suffer from central vestibular dysfunction. Findings in the interval may yield mild signs of damage to both the central vestibular and ocular motor system and to the inner ear. These interictal clinical signs are not specific to VM but can be also observed in migraineurs without a history of vestibular symptoms. How migraine affects the vestibular system is still a matter of speculation. In the absence of high-quality therapeutic trials, treatment is targeted at the underlying migraine.

Loss of heterozygosity in sporadic oesophageal tumors in the tylosis oesophageal cancer (TOC) gene region of chromosome 17q.

From the genotyping of UK and US tylotic families with a high risk of oesophageal cancer we have previously localized the tylosis-associated cancer susceptibility gene (TOC gene, tylosis oesophageal cancer gene) to a 1 cM region on the long arm of chromosome 17 (Kelsell et al., 1996). In the present study we investigated loss of heterozygosity (LOH) patterns of 35 sporadic squamous cell carcinomas of the oesophagus using six polymorphic microsatellite markers encompassing this locus. Twenty-four of the 35 cases (69%) revealed LOH at one or more loci. Deletion was most frequently observed with the marker D17S801 (64% LOH, informative cases), which shows significant linkage to the TOC locus. The LOH analysis in sporadic oesophageal cancer we report here is thus consistent with the hypothesis that the tylosis oesophageal cancer susceptibility gene is also involved in the pathogenesis of a proportion of sporadic squamous cell carcinomas of the oesophagus.

Benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo has been recognized as the most common vestibular disorder. The evolution of its pathophysiological concepts has led to current therapeutic strategies that have made it the most successfully treatable cause of vertigo.

p53 mutations in esophageal tumors from a high incidence area of China in relation to patient diet and smoking history.

Esophageal tumors from 29 patients residing in Guangzhou, China were examined for mutations in exons 5-8 of the p53 tumor suppressor gene and for p53 protein accumulation in tumor cell nuclei. Anamnestic data for each patient, which included information on family history of cancer, tobacco smoking, drinking of alcoholic beverages, and dietary habits such as consumption of pickled vegetables, were recorded. Screening of DNA from tumor cells microdissected from biopsies was performed by PCR amplification of p53 gene exons 5-8, denaturing gradient gel electrophoresis analysis, and DNA sequencing. Mutations were identified in 20 of 29 tumors (69%). All tumors harboring a missense mutation in the p53 gene also showed nuclear accumulation of the tumor suppressor protein by immunohistochemistry. The most common p53 mutations in these tumors were guanine to adenine (G-->A) transitions (10 of 20 tumors; 50%). We did not find multiple mutations at codon 176, in contrast to Lung et al. in their recent study of esophageal cancer patients from Guangzhou (M. L. Lung et al., Cancer Epidemiol. Biomark. Prev., 5: 277-284, 1996). The mutation prevalence was high both in smokers (13 mutations in 20 smokers; 65%) and in nonsmokers (7 of 9 tumors with mutations; 78%), an observation that differs from that of studies in European and North American patients, which demonstrate a much higher prevalence of p53 mutations in smokers than in nonsmokers (reviewed in R. Montesano et al., Int. J. Cancer Predict. Oncol., 69: 225-235, 1996.). Our findings in this pilot study of tumor suppressor gene mutations in patients from Guangzhou support a large body of epidemiological observations pointing to dietary mutagenic carcinogens peculiar to populations in China at high risk of esophageal cancer.

The eye movements of syncope.

We videotaped the eye movements of syncope in 25 healthy volunteers who induced fainting by hyperventilation and Valsalva maneuver on a tilt table. In an additional three subjects, syncope was similarly induced during horizontal sinusoidal oscillation on a rotating chair while eye movements were recorded by electro-oculogram. Fourteen of 25 subjects experienced syncope on the tilt table. Six had downbeat nystagmus (DBN) at the onset that evolved into upward eye deviation, whereas seven showed isolated tonic upward deviation. In one subject the eyes remained in primary position. The gain of the vestibulo-ocular reflex (VOR) increased by 65% on average during syncope with concurrent vestibular stimulation. DBN, upward eye deviation, and increased VOR gain may all be caused by vestibular disinhibition caused by cerebellar hypoperfusion.

Continuous vertigo and spontaneous nystagmus due to canalolithiasis of the horizontal canal.

The authors present a patient with benign paroxysmal positional vertigo of the right horizontal semicircular canal who developed persistent vertigo with spontaneous horizontal nystagmus to the left and caloric hypoexcitability on the right after a head shaking maneuver. Both spontaneous nystagmus and canal paresis resolved after repeated shaking of the head. The most probable mechanism of this type of vertigo is plugging of the horizontal canal by otoconial particles with a negative endolymph pressure between plug and cupula.

The interrelations of migraine, vertigo, and migrainous vertigo.

OBJECTIVE: To assess the prevalence of migrainous vertigo in patients with migraine and in patients with vertigo according to explicit diagnostic criteria that are presented for discussion. METHODS: The authors prospectively evaluated 200 consecutive patients from a dizziness clinic and 200 patients from a migraine clinic for migrainous vertigo based on the following criteria: 1) recurrent vestibular symptoms (rotatory/positional vertigo, other illusory self or object motion, head motion intolerance); 2) migraine according to the criteria of the International Headache Society (IHS); 3) at least one of the following migrainous symptoms during at least two vertiginous attacks: migrainous headache, photophobia, phonophobia, visual or other auras; and 4) other causes ruled out by appropriate investigations. In addition, the authors compared the prevalence of migraine according to the IHS criteria in the dizziness clinic group with a sex- and age-matched control group of 200 orthopedic patients. RESULTS: The prevalence of migraine according to the IHS criteria was higher in the dizziness clinic group (38%) compared with the age- and sex-matched control group (24%, p < 0.01). The prevalence of migrainous vertigo was 7% in the dizziness clinic group, and 9% in the migraine clinic group. In 15 of 33 patients with migrainous vertigo, vertigo was regularly associated with migrainous headache. In 16 patients, vertigo occurred both with and without headache, and in two patients headache and vertigo never occurred together. The duration of attacks varied from minutes to days. CONCLUSION: These results substantiate the epidemiologic association between migraine and vertigo and indicate that migrainous vertigo affects a significant proportion of patients both in dizziness and headache clinics.

A modified Epley's procedure for self-treatment of benign paroxysmal positional vertigo.

We compared the efficacy of a modified Epley's procedure (MEP) and Brandt-Daroff exercises (BDE) for self-treatment of benign paroxysmal positional vertigo of the posterior semicircular canal (PC-BPPV) in 54 patients. PC-BPPV resolved within 1 week in 18 of 28 patients (64%) using the MEP and in 6 of 26 patients (23%) performing BDE (p<0.01). Type and adequate performance of the maneuver predicted treatment outcome in the multivariate analysis. The frequency of side effects was not significantly different between the two groups. The MEP is more suitable for self-treatment of PC-BPPV than conventional BDE.

Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit.

OBJECTIVE: To determine the extent that demographics, clinical characteristics, comorbidities, and complications contribute to the risk of in-hospital mortality and morbidity in acute stroke. METHODS: Data of consecutive patients admitted to 14 stroke units cooperating within the Berlin Stroke Register were analyzed. The association of demographics, clinical characteristics, comorbidities, and complications with the risk of in-hospital death and poor outcome at discharge was assessed, and independent attributable risks were calculated, applying average sequential attributable fractions. RESULTS: In a 3-year period, 16,518 consecutive patients with ischemic or hemorrhagic stroke were documented. In-hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale score ≥3). In patients with length of stay (LOS) ≤7 days, 37.5% of in-hospital deaths were attributed to stroke severity, 23.1% to sociodemographics (age and prestroke disability), and 28.9% to increased intracranial pressure (iICP) and other complications. In those with LOS >7 days, age and stroke severity accounted for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP (8.3%) contributed to one-third of in-hospital deaths. For poor outcome, attributable risks were similar for prestroke disability, stroke severity, pneumonia, and other complications regardless of the patient's LOS. CONCLUSIONS: Approximately two-thirds of early death and poor outcome in acute stroke is attributed to nonmodifiable predictors, whereas main modifiable factors are early complications such as iICP, pneumonia, or other complications, on which stroke unit treatment should focus to further improve the prognosis of acute stroke.

Migrainous vertigo: prevalence and impact on quality of life.

OBJECTIVE: To investigate the epidemiology of migrainous vertigo (MV) in the general population by assessing prevalence, clinical features, comorbid conditions, quality of life, and health care utilization. METHODS: We screened a representative sample of the adult population in Germany (n = 4,869) for moderate or severe dizziness/vertigo and followed up with validated neurotologic telephone interviews (n = 1,003). Diagnostic criteria for MV were as follows: 1) recurrent vestibular vertigo; 2) migraine according to the International Headache Society; 3) migrainous symptoms during at least two vertiginous attacks (migrainous headache, photophobia, phonophobia, or aura symptoms); and 4) vertigo not attributed to another disorder. In a concurrent validation study (n = 61) the interviews had a sensitivity of 84% and a specificity of 94% for vestibular vertigo and 81% and 100% for migraine. RESULTS: The lifetime prevalence of MV was 0.98% (95% CI 0.70 to 1.37), the 12-month prevalence 0.89% (95% CI 0.62 to 1.27). Spontaneous rotational vertigo was reported by 67% of participants with MV while 24% had positional vertigo. Twenty-four percent always experienced headaches with their vertigo. Logistic regression analysis comparing participants with MV with dizziness-free migraineurs showed an independent association with coronary heart disease but not with sex, age, migrainous aura, education, stroke, hypertension, hyperlipidemia, body mass index, or depression. Age-adjusted health-related quality of life scores (SF-8 Health Survey) were consistently lower in participants with MV compared to dizziness-free controls. Two thirds of participants with MV had consulted a doctor but only 20% of these were diagnosed with MV. CONCLUSIONS: Migrainous vertigo is relatively common but underdiagnosed in the general population and has considerable personal and healthcare impact.

Epidemiology of vestibular vertigo: a neurotologic survey of the general population.

OBJECTIVE: The purpose of this study was to determine the prevalence and incidence of vestibular vertigo in the general population and to describe its clinical characteristics and associated factors. METHODS: The neurotologic survey had a two-stage general population sampling design: nationwide modified random digit dialing sampling for participation in the German National Telephone Health Interview Survey 2003 (response rate 52%) with screening of a random sample of 4,869 participants for moderate or severe dizziness or vertigo, followed by detailed neurotologic interviews developed through piloting and validation (n = 1,003, response rate 87%). Diagnostic criteria for vestibular vertigo were rotational vertigo, positional vertigo, or recurrent dizziness with nausea and oscillopsia or imbalance. Vestibular vertigo was detected by our interview with a specificity of 94% and a sensitivity of 84[corrected]% in a concurrent validation study using neurotology clinic diagnoses as an accepted standard (n = 61). RESULTS: The lifetime prevalence of vestibular vertigo was 7.4[corrected]%, the 1-year prevalence was 4.9[corrected]%, and the incidence was 1.4[corrected]%. In 80% of affected individuals, vertigo resulted in a medical consultation, interruption of daily activities, or sick leave. Female sex, age, lower educational level, and various comorbid conditions, including tinnitus, depression, and several cardiovascular diseases and risk factors, were associated with vestibular vertigo in the past year in univariate analysis. In multivariable analysis, only female sex, self-reported depression, tinnitus, hypertension, and dyslipidemia had an independent effect on vestibular vertigo. CONCLUSIONS: Vestibular vertigo is common in the general population, affecting [corrected] 5% of adults in 1 year. The frequency and health care impact of vestibular symptoms at the population level have been underestimated.